1,1'-Carbonyldiimidazole → 5-Chloro-N-[2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]oct-3-yl]-2-methoxy-4-(methylamino)benzamide

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Reaction Steps

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.35 g, 15.5 mmoles) in anhydrous tetrahydrofuran (20 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.56 g, 15.8 mmoles), and stirred for one hour at room temperature. Nitrogen was bubbled through the solution for 20 minutes, and a solution of 2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]-octan-3-amine (3.95 g, 15.8 mmoles) in tetrahydrofuran (10 ml) was added dropwise. The mixture was maintained at room temperature for 18 hours, and at 50° C. for 1 hour, then concentrated in vacuo. The residue was partitioned between methylene chloride and 1.0N aqueous sodium carbonate, and the organic layer was separated. The aqueous solution was extracted with methylene chloride, and the combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was filtered through alumina (eluted with 3% methanol/methylene chloride) to provide 5.38 g (79%) of a colorless foam.

Provenance & Evidence